tbuckley/cabot-search huggingface dataset:
Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea
Authors: Matthew C. Baker, Khushboo Sheth, Yuhan Liu, Di Lu, Rong Lu, William H. Robinson
Journal: JAMA Network Open (2023)

Metformin may have a protective association against developing osteoarthritis (OA), but robust epidemiological data are lacking.To determine the risk of OA and joint replacement in individuals with type 2 diabetes treated with metformin compared with a sulfonylurea.This retrospective cohort study used claims data from the Optum deidentified Clinformatics Data Mart Database between December 2003 and December 2019. Participants included individuals aged 40 years or older with at least 1 year of continuous enrollment and type 2 diabetes. Individuals with type 1 diabetes or a prior diagnosis of OA, inflammatory arthritis, or joint replacement were excluded. Time-conditional propensity score matching was conducted using age, sex, race, Charlson comorbidity score, and treatment duration to create a prevalent new-user cohort. Data were analyzed from April to December 2021.Treatment with metformin or a sulfonylurea.The outcomes of interest were incident OA and joint replacement. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) of incident OA and joint replacement. In a sensitivity analysis, individuals only ever treated with metformin were compared with individuals only ever treated with a sulfonylurea, allowing for longer-term follow up of the outcome (even after stopping the medication of interest).After time-conditional propensity score matching, the metformin and control groups each included 20 937 individuals (mean [SD] age 62.0 [11.5] years; 24 379 [58.2%] males). In the adjusted analysis, the risk of developing OA was reduced by 24% for individuals treated with metformin compared with a sulfonylurea (aHR, 0.76; 95% CI, 0.68-0.85; P < .001), but there was no significant difference for risk of joint replacement (aHR, 0.80; 95% CI, 0.50-1.27; P = .34). In the sensitivity analysis, the risk of developing OA remained lower in individuals treated with metformin compared with a sulfonylurea (aHR, 0.77; 95% CI, 0.65-0.90; P < .001) and the risk of joint replacement remained not statistically significant (aHR, 1.04; 95% CI, 0.60-1.82; P = .89).In this cohort study of individuals with diabetes, metformin treatment was associated with a significant reduction in the risk of developing OA compared with sulfonylurea treatment. These results further support preclinical and observational data that suggest metformin may have a protective association against the development of OA; future interventional studies with metformin for the treatment or prevention of OA should be considered.
Incidence of Interstitial Lung Disease in Patients With Rheumatoid Arthritis Treated With Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs
Authors: Matthew C. Baker, Yuhan Liu, Rong Lu, Janice Lin, Jason Melehani, William H. Robinson
Journal: JAMA Network Open (2023)

Importance Current data are lacking regarding the risk of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use on the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Objective To determine the risk of developing ILD in patients with RA undergoing treatment with different b/tsDMARDs. Design, Setting, and Participants Retrospective cohort study using claims data from the Optum Clinformatics Data Mart between December 2003 and December 2019. Adult patients with RA, 1 year or more of continuous enrollment, treatment with a b/tsDMARD of interest, and without preexisting ILD were included. Data were analyzed from October 2021 to April 2022. Exposures New administration of adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib. Main Outcomes and Measures Crude incidence rates (IRs) for the development of ILD were calculated. The risk of ILD across different b/tsDMARDs was compared using Cox-regression models. A sensitivity analysis using a prevalent new-user cohort design compared patients treated with tofacitinib and adalimumab. Results A total of 28 559 patients with RA (mean [SD] age 55.6 [13.7] years; 22 158 female [78%]) were treated with adalimumab (13 326 patients), abatacept (5676 patients), rituximab (5444 patients), tocilizumab (2548 patients), or tofacitinib (1565 patients). Crude IRs per 1000 person-years for ILD were 3.43 (95% CI 2.85-4.09) for adalimumab, 4.46 (95% CI 3.44-5.70) for abatacept, 6.15 (95% CI 4.76-7.84) for rituximab, 5.05 (95% CI 3.47-7.12) for tocilizumab, and 1.47 (95% CI 0.54-3.27) for tofacitinib. After multiple adjustments, compared with patients treated with adalimumab, patients treated with tofacitinib had a lower risk of ILD (adjusted hazard ratio [aHR] 0.31; 95% CI, 0.12-0.78; P = .009). In a prevalent new-user cohort analysis, patients treated with tofacitinib had 68% reduced risk of ILD compared with adalimumab (aHR 0.32; 95% CI 0.13-0.82; P &amp;amp;lt; .001). In an adjusted model, there was a 69% reduced risk of ILD in patients treated with tofacitinib compared with patients treated with adalimumab. Conclusions and Relevance In this retrospective cohort of patients with RA, patients treated with tofacitinib had the lowest incidence of ILD compared with patients treated with all bDMARDs evaluated, and patients treated with tofacitinib had a reduced risk of ILD compared with patients treated with adalimumab after adjusting for important covariates. Additional prospective studies are needed to better understand the role tofacitinib may play in preventing ILD in patients with RA. These results, while significant, should be interpreted with caution given the fairly small sample size of the tofacitinib group.
Perioperative Risk Assessment and Avoiding Overuse of Anesthesia Care for Routine Cataract Surgery
Authors: Adam A. Dalia, Timothy Houle, Jeanine Wiener-Kronish
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Knowledge to Advance the Clinical Effectiveness of Pediatric Complex Care
Authors: Jay G. Berry, Chris Feudtner
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Multiple myeloma with t(11;14): impact of novel agents on outcome
Authors: Borja Puertas, Verónica González-Calle, Eduardo Sobejano-Fuertes, Fernando Escalante, Beatriz Rey-Bua, Irene Padilla, Ramón García-Sanz, Noemi Puig, Norma C. Gutiérrez, María-Victoria Mateos
Journal: Blood Cancer Journal (2023)

Abstract Multiple myeloma (MM) patients with t (11;14) present unique biological features and their prognosis is not well established. We report a retrospective study of 591 MM patients, 17.3% of whom had t (11;14). It was designed to determine the prognostic impact of this abnormality and the effect of novel agents on the response and outcomes. Three groups were established based on their cytogenetics: (1) t (11;14); (2) high-risk chromosomal abnormalities; and (3) standard risk (SR). After 80.1 months (1.2–273.8 months) of follow-up, no differences were observed in overall survival (OS) between the t (11;14) and SR groups (75.8 vs. 87.2 months; P = 0.438). Treatment of MM t (11;14) with novel agents did not improve their overall response rate (ORR) or complete response (CR) compared with those who received conventional therapy (ORR: 87.2 vs. 79.5%, P = 0.336; CR: 23.4 vs. 12.8%, P = 0.215). This effect translated into a similar PFS (39.6 vs. 30.0 months; P = 0.450) and OS (107.6 vs. 75.7 months; P = 0.175). In summary, MM t (11;14) patients did not benefit from the introduction of novel agents as much as SR patients did, indicating that other therapies are needed to improve their outcomes.
Experiences of Organizational Practices That Advance Women in Health Care Leadership
Authors: Mariam Mousa, Belinda Garth, Jacqueline A. Boyle, Kathleen Riach, Helena J. Teede
Journal: JAMA Network Open (2023)

Importance Women are underrepresented in health care leadership positions. Organizational practices and culture play a key role in mitigating this disparity. Objective To explore the experiences of women in leadership roles and inform how health care organizations can support the advancement of women into leadership. Design, Setting, and Participants This qualitative study used a constructivist grounded theory approach applied over a 1-year period (May 1, 2021, to May 31, 2022) in a large private health care network in Australia. Women were eligible if they had been in leadership positions for more than 5 years. Purposive and theoretical sampling guided recruitment of 28 women, representing medical, nursing, and allied health specialties. Interviews lasted 1 hour, producing 500 pages of transcripts for analysis. Main Outcomes and Measures The primary outcome was a model of organizational practices and conditions that advance women in health care leadership, extrapolated from the collective experiences of women in leadership. Key elements pertained to organizational patterns of interaction and group norms and behaviors that contributed toward women’s experiences of career advancement. Results Overall, 28 women (23 [82%] White; 3 [11%] Southeast Asian) participated in the study, 10 (36%) of whom were in nursing, 9 (32%) of whom were in allied health, and 9 (32%) of whom were in medical disciplines. Organizational practices that advance women in health care leadership were highly dependent on conducive organizational culture enhancing women’s credibility and capability as leaders. Four interrelated elements were identified that create the necessary conditions for an organizational culture to advance women in health care leadership, including (1) identifying and actively addressing systemic barriers, (2) challenging gendered assumptions and expectations of leadership behaviors, (3) providing mentorship to shape career opportunities, and (4) determining how these conditions all contribute toward raising women’s credibility to enable internalizing a leadership identity. For women, advancing to leadership involved organizations moving away from ad hoc, inconsistent applications of gender equity practices and generating supportive practices that reinforced a workforce culture of credibility, collaboration, and continuous improvement to support women. Conclusions and Relevance In light of persisting inequity in health care leadership, women’s experiences were captured in this qualitative study to identify organizational practices that support their advancement. Insights into factors that influence efficacy of these practices, including building a supportive culture and mentoring, are discussed. This research informs a National Health and Medical Research Council initiative with international collaborators to support organizations in advancing women in health care leadership.
NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer
Authors: Ruihui Xie, Liang Cheng, Ming Huang, Lin Huang, Ziyue Chen, Qiang Zhang, Hong Li, Junlin Lu, Hongjin Wang, Qianghua Zhou, Jian Huang, Xu Chen, Tianxin Lin
Journal: Cancer Research (2023)

Abstract Epitranscriptomic RNA modifications constitute a critical gene regulatory component that can affect cancer progression. Among these, the RNA N4-acetylcytidine (ac4C) modification, which is mediated by the ac4C writer N-acetyltransferase 10 (NAT10), regulates the stabilization of mRNA. Here, we identified that the ac4C modification is induced upon cisplatin treatment and correlates with chemoresistance in bladder cancer. Both in vitro and in vivo, NAT10 promoted cisplatin chemoresistance in bladder cancer cells by enhancing DNA damage repair (DDR). Mechanistically, NAT10 bound and stabilized AHNAK mRNA by protecting it from exonucleases, and AHNAK-mediated DDR was required for NAT10-induced cisplatin resistance. Clinically, NAT10 overexpression was associated with chemoresistance, recurrence, and worse clinical outcome in patients with bladder cancer. Cisplatin-induced NFκB signaling activation was required for the upregulation of NAT10 expression, and NFκB p65 directly bound to the NAT10 promoter to activate transcription. Moreover, pharmacological inhibition of NAT10 with Remodelin sensitized bladder cancer organoids and mouse xenografts to cisplatin. Overall, the present study uncovered a mechanism of NAT10-mediated mRNA stabilization in bladder cancer, laying the foundation for NAT10 as a therapeutic target to overcome cisplatin resistance in bladder cancer. Significance: The mRNA ac4C writer NAT10 stimulates DNA damage repair to promote cisplatin chemoresistance in bladder cancer, identifying NAT10 inhibition as a potential therapeutic approach to enhance cisplatin sensitivity.
<i>JAMA Internal Medicine</i>—The Year in Review, 2022
Authors: Rita F. Redberg
Journal: JAMA Internal Medicine (2023)

The US enters the fourth year of the COVID-19 pandemic with increasing health care challenges.Medicare is heading toward insolvency, launch prices of new drugs are reaching an all-time high, and Congress is increasingly dysfunctional.At JAMA Internal Medicine, our hard work of promoting highvalue health care that is accessible to all is more important than ever.Meanwhile, we are continuing to watch closely the implementation phase of reducing low-value care.The journal's Less is More series of articles, which is entering its 13th year, is as important as ever.In 2023, we hope to see progress on complex issues such as value-based payment, drug pricing, and transparency of data and regulatory decisions, to name just a few.We continue to inform our readership and propose solutions to increase highvalue care.For JAMA Internal Medicine, 2022 was a banner year in many ways.The journal's impact factor soared to an all-time high of 44.46, climbing from lower than 10 when I started as Editor in 2009.On behalf of the entire incredible editorial team, we appreciate this recognition (and many others) of the importance and relevance of the articles we publish to the practice and to health care.2][3][4][5][6][7] The most-viewed article of 2022 was a study of ivermectin treatment for patients with COVID-19, 1 notable for both most views and downloads, as well as the highest Altmetric attention score.This randomized clinical trial found that ivermectin treatment during early illness did not prevent progression to severe disease among high-risk adult patients with mild to moderate COVID-19.Despite lack of evidence of benefit, use of this drug for treatment of COVID-19 continues.Thanks to the hard work of the amazing editorial team and triage led by Editor at Large and Online Editor Robert Steinbrook, MD, the turnaround times both for days from receipt to first decision without peer review as well as with peer review and all other turnaround times remain fast (Table ).We love hearing stories about how publishing in JAMA Internal Medicine boosted authors' careers, helped get a grant or important committee assignment, or helped in clinical practice.And others want to read this work in JAMA Internal Medicine, as there were 13.8 million downloads and more than 26 000 media mentions of JAMA Internal Medicine articles-the journal's highest ever.We strive to publish articles that will help in the practice of medicine, including for the care of patients with COVID-19, either teaching something new to improve outcomes or a practice to avoid for lack of benefit.We will continue to publish articles on the daily challenges in health care and medicine and focus on ways to improve the experience for clinicians and patients, as well as approaches to improve the health care system.
Acute-on-chronic liver failure: Terminology, mechanisms and management
Authors: Vinay Kumar BR, Shiv Kumar Sarin
Journal: Clinical and Molecular Hepatology (2023)

Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, gives an opportunity for reversal of the syndrome. Scores like the Asian Pacific Association for the Study of the Liver (APASL) ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade hepatic encephalopathy, and in the absence of >2 organ failure or overt sepsis to improve survival of up to 80% at five years. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.
Six-Year Cognitive Trajectory in Older Adults Following Major Surgery and Delirium
Authors: Zachary J. Kunicki, Long H. Ngo, Edward R. Marcantonio, Douglas Tommet, Yi Feng, Tamara G. Fong, Eva M. Schmitt, Thomas G. Travison, Richard N. Jones, Sharon K. Inouye
Journal: JAMA Internal Medicine (2023)

Importance The study results suggest that delirium is the most common postoperative complication in older adults and is associated with poor outcomes, including long-term cognitive decline and incident dementia. Objective To examine the patterns and pace of cognitive decline up to 72 months (6 years) in a cohort of older adults following delirium. Design, Setting, and Participants This was a prospective, observational cohort study with long-term follow-up including 560 community-dwelling older adults (older than 70 years) in the ongoing Successful Aging after Elective Surgery study that began in 2010. The data were analyzed from 2021 to 2022. Exposure Development of incident delirium following major elective surgery. Main Outcomes and Measures Delirium was assessed daily during hospitalization using the Confusion Assessment Method, which was supplemented with medical record review. Cognitive performance using a comprehensive battery of neuropsychological tests was assessed preoperatively and across multiple points postoperatively to 72 months of follow-up. We evaluated longitudinal cognitive change using a composite measure of neuropsychological performance called the general cognitive performance (GCP), which is scaled so that 10 points on the GCP is equivalent to 1 population SD. Retest effects were adjusted using cognitive test results in a nonsurgical comparison group. Results The 560 participants (326 women [58%]; mean [SD] age, 76.7 [5.2] years) provided a total of 2637 person-years of follow-up. One hundred thirty-four participants (24%) developed postoperative delirium. Cognitive change following surgery was complex: we found evidence for differences in acute, post–short-term, intermediate, and longer-term change from the time of surgery that were associated with the development of postoperative delirium. Long-term cognitive change, which was adjusted for practice and recovery effects, occurred at a pace of about −1.0 GCP units (95% CI, −1.1 to −0.9) per year (about 0.10 population SD units per year). Participants with delirium showed significantly faster long-term cognitive change with an additional −0.4 GCP units (95% CI, −0.1 to −0.7) or −1.4 units per year (about 0.14 population SD units per year). Conclusions and Relevance This cohort study found that delirium was associated with a 40% acceleration in the slope of cognitive decline out to 72 months following elective surgery. Because this is an observational study, we cannot be sure whether delirium directly causes subsequent cognitive decline, or whether patients with preclinical brain disease are more likely to develop delirium. Future research is needed to understand the causal pathway between delirium and cognitive decline.
Soyon Hong: My role is to empower
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2023)

Soyon Hong is a group leader at the UK Dementia Research Institute at UCL. Her lab is interested in investigating how multiple cell types work together to maintain brain function, and how these interactions are affected and altered in neurodegenerative disease states such as Alzheimer's disease. Here, Soyon talks about how she got interested in science, what she's currently working on, and the importance of good mentorship throughout your academic career.